Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus

Background. The plasma concentrations of total homocysteine (tHcy) and tota l cysteine (tCys) are determined by intracellular metabolism and by renal p lasma clearance, and we hypothesized that glomerular filtration is a major determinant of plasma tHcy and tCys. We studied the relationships between t he glomerular filtration rate (GFR) and plasma tHcy and tCys in populations of diabetic patients with particularly wide ranges of GFR. Methods. We measured GFR, urine albumin excretion rate (UAER), plasma tHcy, tCys, methionine, vitamin B-12, folate, C-peptide, and routine parameters in 50 insulin-dependent diabetes mellitus (IDDM) and 30 non-insulin-depende nt diabetes mellitus (NIDDM) patients. All patients underwent intensive ins ulin treatment and had a serum creatinine concentration below 115 mu mol/li ter. Results. Mean plasma tHcy in diabetic patients (0.1 mu mol/liter) was lower than in normal persons (11.1 mu mol/liter, P = 0.0014). Mean plasma tCys i n diabetic patients (266.1 mu mol/liter) was also lower than in normal pers ons (281.9 mu mol/liter, P = 0.0005). Seventy-three percent of the diabetic patients had relative hyperfiltration. Plasma tHcy and tCys were closely a nd independently associated with GFR, serum folate, and serum B12. However, plasma tHcy was not independently associated with any of the 22 other vari ables tested, including age, serum creatinine concentration, UAER, total da ily insulin dose, and glycemic control. Conclusions. Glomerular filtration rate is an independent determinant of pl asma tHcy and tCys concentrations, and GFR is rate limiting for renal clear ance of both homocysteine and cysteine in diabetic patients without overt n ephropathy. Declining GFR explains the age-related increase in plasma tHcy, and hyperfiltration explains the lower than normal mean plasma tHcy and tC ys concentrations in populations of diabetic patients.